Here we shall have a discussion of an
important topic called amyloidosis.
It’s short and sweet, to the point,
and must understand as to how
amyloidosis works in our body
and how it manifests. Let’s begin.
So what is amyloidosis? Well at first, I’m
going to walk you through the pathologic
appearance of amyloid and how
you must interpret it.
So the pathologic deposition
of distinct protein
in the extracellular space.
Appearance wise, if you were to take a look
at it without proper staining,
you see the areas that
are rather thickened.
There are areas that you find to be
thickened will be deposition of amyloid,
we’ll just call this emorphous.
Now you suspect amyloid deposition, why?
Well, I’ll walk you through
some differentials later,
including diabetes type 2,
And at this point, you might be thinking
about using Congo red stain,
and when you find your Conga red stain
then the color of your amyloid
that you’d expect to find,
would then be red or pink.
And then you’d do what’s known as
a polarized microscopy,
and when you do so, then you would find
this to be apple-green birefringent.
The last time we had any
discussion of birefringent
was when we had our discussion
of gout versus calcium
Now what this picture is trying to tell us,
is the fact that each one of these columns,
are ways in which you may then
accumulate commonly amyloid.
I say commonly because as we get older,
we have senile amyloid that
could then develop.
So what you’re seeing here on the left
is that if there was a process
that was a misfolded issue,
and if there was a misfolded
protein, such as for example
protein Huntington in Huntington disease,
or even let’s say CFTR,
cystic fibrosis and such.
Then the type of amyloid that
may develop is fibril.
And the production of abnormal
amounts of protein,
this might have occurred due to maybe
disease processes or chronic inflammation.
Or let’s say that there is something
like plasma cell dyscrasia,
what does that mean? For example,
you’ve heard of multiple myeloma,
lytic bone lesions and so forth, right?
And here, later on, we’ll talk
about how you may then be
using too much of the light chain,
in particular light chain
that produced a lot more would be kappa.
Anyhow, point is, you would then be
producing your amyloid light protein.
Whereas if it is chronic
type of inflammation,
then you would call this amyloid
protein or AA protein.
As we get older, there is every possibility
that we may then just be accumulating
normal transthyretin. ATTR
stands for transthyretin
and the A standing for amyloid.
These are, in general,
different types of amyloids that
you would then be forming on, well
patients that you would see quite commonly
for one reason or another or
encounter in a clinical scenario,
or clinical conference,
what have you.
The primary amyloidosis that
we will take a look at.
Let’s say that your patient
did have lytic bone lesion,
was a patient who was a male
above the age of 50,
and upon bone marrow aspirate ended up
finding these plasma cells,
and tons of them.
Well you might be thinking of myeloma as
being one of your differentials.
You can take a look at the picture over
to the right then you do remember
the anatomy of an immunoglobulin,
and immunoglobulin—I want you to
focus on the following:
You have a heavy chain and light chain,
please identify the light chain.
The light chains in your
plasma cell dyscrasia
will start being increased in production.
If its multiple myeloma, if you remember,
then it’d be either IgG or IgA, not IgM,
and these light chains are then referred
to as your amyloid light chains,
and amyloid light chains may
then deposit on the glomeruli,
and when they do, you do
the Congo red stain,
even the fluorescents as such,
and then you end up finding your
apple-green birefringent, correct?
And some of these light chains may then
filter through, and when they do
in the urine, you would then call
this Bence Jones proteins
as you’re quite familiar with,
associated with plasma cell disorders.
Multiple myeloma would be one of them
and Waldenstrom macroglobulinemia
also known as lymphoplasmacytic lymphoma,
then it’d be IgM or perhaps other B-cell
In general, light chains is what we’re
looking at here, AL primary type.
If there’s deposition of amyloid fibrils,
then this is then derived from
your Ig lambda light chains
is what you’re going to call this.
The amyloid light chains
produced by plasma cells
in multiple myeloma and Waldenstrom like
we just said is our differentials.
The specific amyloidosis
that you want to know,
for sure, will be the following.
If a patient gets older
and starts forgetting,
obviously thinking about Alzheimer’s
is a big problem.
With Alzheimer’s, you should
be extremely familiar with
amyloid beta protein.
Remember that each one of
us are depositing tau,
the taw would then be of course being
your little spindles and such,
and these are tangles that
we deposit—all of us do,
doesn’t correlate with the
severity of the disease,
but the more number of these
tau tangles that we deposit,
then you worry about amyloid aren’t you?
Or in other words, Alzheimer’s.
Whereas now, if you’re talking
about the amyloid,
then you should be referring to
the beta amyloid plaques.
The beta amyloid plaque is what we then
call amyloid precursor protein (APP)
Commit that to memory.
And then gene for precursor
is on the protein of c21—keep
that in mind—c21.
Since APP gene is located on chromosome 21,
individuals with Down syndrome have
an increased lifetime prevalence
of Alzheimer’s disease.
If you have a patient who has a constellation
of symptoms of maybe hypercalcemia,
also has episodic hypertension,
and in the urine you then find acid,
and then on a szintigramm of the
thyroid you find a cold nodule.
Well what I gave you here was MEN 2a.
Again you have a parathyroidism
I gave you chromocytoma,
and here am giving you medullary
cancer of the thyroid.
In medullary cancer of the thyroid,
the type of amyloid
deposit derived from calcitonin
because of peripheral B cell
producing too much calcitonin.
In type 2 diabetes, the type of amyloid
derivative that you’re looking for
is then called your well
amyloid polypeptide or islet.
I, A—amyloid, P—poly,
P—peptide. Often times you’ll
see the abbreviation IAPP,
sometimes referred to as being amylin.
Now please make sure that you’re
quite familiar with knowing that
type 2 diabetes mellitus
the type that often times, the pathogenesis,
being referred to with
where the receptors aren’t working. You
with me? Especially as we get obese.
So therefore, or should I say, when I get
obese —I can’t speak on your behalf
is amylin or islet amyloid polypeptide
is a particular amyloid derivative
you want to keep in mind.
For amyloidosis, there is a huge variety
of symptoms that can present with.
In the renal system, you can have
or nephrotic syndrome.
Looking on the cardiac system,
there might be a heart failure,
arrhythmia, or heart block.
In the GIT, it can result in hepatomegaly.
There are also neurological symptoms
like peripheral neuropathy
with CNS involvement such as
vision or hearing loss is rare.
In the musculoskeletal system,it can
result in pseudohypertrophy.
You can have a big amount of bleeding
due to reduced factor 10 activity.
In the respiratory system, there might be
persistent pulmonary effusions,
nodules, or pulmonary hypertension.
And lastly on the skin, there might
be subcutaneous nodules.